The present invention relates to compounds having pharmaceutical properties, and in particular, to compounds having muscle relaxant properties. More specifically, the present invention relates to muscle relaxant compositions and to methods for providing muscle relaxation.
Various compounds having muscle relaxant properties are set forth in U.S. Pat. Nos. 4,190,674 to Grivsky; 4,508,715 to Booth et al; 4,7611,418 to Swaringen, Jr. et al; 4,701,460 to El-Sayad et al; 4,179,507 to Stenlake et al; 4,923,898 to Sunshine et al; 5,015,741 to Osdene el al and 5,260,337 to Sims et al.; as well as in Goodmau and Gilman's The Pharmacological Basis of Therapeutics. Chapters 5 and 6, 6th Edit. (1980) and Physicians Desk Reference, 48 Edit., pp. 689, 758, 1362 and 1648 (1994).
Compounds having musculoskeletal relaxing properties include (1) agents acting in the central nervous system which are used to relieve pain associated with muscle contraction (e.g., 5-chlorobenzoxazolinone available as Parafon Forte DSC from McNeil Pharmaceutical), and (2) agents acting in the peripheral nervous system used primarily to induce muscle relaxation and hence reduce muscle contraction during anesthesia. The second group of muscle relaxants is subdivided into two groups: (i) non-depolarizing agents which inhibit the activation of muscle receptors (e.g., metocurarine iodide, d-tubocurarine, tubocurarine chloride, pancuronium, gallamine, diallytoiferine, toxiferine, atracurium besylate which is available as Tracrium from Burroughs-Wellcome Co., and vecuronium bromide which is available as Norcuron from Organon Inc.) and (ii) depolarizing agents which transiently activate muscle receptors and result in their blockade (e.g., decamethonium iodide, and succinylcholine chloride which is available as Anectine from Burroughs-Wellcome Co.). The effects of the depolarizing agents are manifested as fasciculations and flaccid paralysis which are observed to occur rapidly after their injection.
The effects of depolarizing agents (DA) and non-depolarizing agents (NDA) are separated based on their duration of action from ultrashort acting (e.g. for a depolarizing agent such as succinylcholine chloride) to intermediate (e.g..for a non-depolarizing agent such as atracurium besylate). Certain types of muscle relaxants are useful as neuromuscular blocking agents in clinical applications, and have found use as adjuvants to surgical anesthesia, in orthopedic surgical procedures and in facilitating endotracheal intubation procedures. Some of these compounds (e.g., succinylcholine chloride) are routinely used to provide muscle relaxation during Cesarean section procedures.
It is desirable for neuromuscular blocking agents to be locally acting and highly selective for binding to muscle nicotinic acetylcholine receptor sites. As such, when a patient is treated with anesthesia, the muscle relaxant is applied (e.g., intravenously or by injection), in order to cause the muscle to relax and hence minimize muscle contraction.
It would be desirable to provide a compound useful as a muscle relaxant. In particular, it would be desirable to provide an agonist which has activity at relatively low concentrations as a neuromuscular blocking agent. It would also be desirable to achieve muscle relaxation at concentrations of agonist that are devoid of any ganglionic effects (e.g., so as to not exhibit side effects such as those associated with interaction with cardiovascular sites). As such, it would be desirable to provide muscle relaxant compositions and methods for providing muscle relaxation.